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Study of Gemcitabine/Carboplatin First-line Chemotherapy +/- Apatorsen in Advanced Squamous Cell Lung Cancers

Information source: Queen Mary University of London
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Squamous Cell Lung Cancer

Intervention: Apatorsen (OGX-427) (Drug); Gemcitabine (Drug); Carboplatin (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Queen Mary University of London

Official(s) and/or principal investigator(s):
Peter Schmid, Prof., Study Chair, Affiliation: Queen Mary University London

Overall contact:
Christine James, Phone: 02078828490, Email: CEDAR@qmcr.qmul.ac.uk


This study is being carried out to see if a new drug called Apatorsen in combination with standard gemcitabine/carboplatin chemotherapy is effective in treating squamous cell lung cancer. This study is part of a research project for collecting information about the effectiveness and safety of Apatorsen when used with gemcitabine/carboplatin chemotherapy. The main purpose of this study is to see if Apatorsen, when combined with gemcitabine/carboplatin, is an effective treatment for squamous cell lung cancer. Recent research has found that a protein called Hsp27 can help cancer cells protect themselves against the effects of cancer treatments. Hsp27 is only found in some lung cancers but when it is present, cancer drugs might not work as well as they would without Hsp27 being present. Blocking the action of Hsp27 or removing Hsp27 from cancer cells with Apatorsen may slow down or stop the cancer growing. This study will therefore look at the relationship between the Hsp27 levels in tumour and blood and the effect of the treatment. The development of Apatorsen is intended to provide a new treatment option for patients with cancer. Apatorsen may also make the cancer more sensitive to gemcitabine and carboplatin and so make this chemotherapy treatment more effective.

Clinical Details

Official title: A Phase II Randomised, Open-label Study of Gemcitabine/Carboplatin First-line Chemotherapy in Combination With or Without the Antisense Oligonucleotide Apatorsen (OGX-427) in Advanced Squamous Cell Lung Cancers

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Progression-Free Survival as measured by investigator-assessed (using RECIST 1.1) progression-free survival

Secondary outcome:

Clinical Activty as measured by response rate (RECIST 1.1), change in tumour size, disease control rate, and duration of response of gemcitabine/carboplatin + Apatorsen relative to gemcitabine/carboplatin alone

Overall survival benefit of gemcitabine/carboplatin + Apatorsen relative to gemcitabine/carboplatin alone

Clinical benefit as measured by investigator assessment using RECIST 1.1

Drug exposure measured as average dose per week

Compare the differences in health-related Quality of Life (HRQL) and symptoms for patients by treatment assignment as measured by the Functional Assessment of Cancer Therapy-Lung (FACT-L) scale, and the Euro-QOL 5D (EQ-5D)

Establish the safety and tolerability of gemcitabine/carboplatin + Apatorsen relative to gemcitabine/carboplatin alone

Detailed description: This is an open-label, multicentre, 2-arm randomised phase II trial of gemcitabine/carboplatin + Apatorsen (OGX-427) versus gemcitabine/carboplatin alone in patients with previously untreated advanced squamous cell lung cancers. Patients will be randomised (1: 1) to one of the two treatment arms:

- Gemcitabine/carboplatin

- Gemcitabine/carboplatin + Apatorsen (OGX-427)

Randomisation will be stratified by the following criteria:

- Stage (IIIB versus IV versus recurrent disease)

- Performance status (0 or 1 versus 2) Gemcitabine/carboplatin chemotherapy will be

continued for 6 cycles unless there is evidence of unacceptable toxicity, disease progression, or if the patient requests that study treatment be discontinued or to be withdrawn from the study. If chemotherapy is discontinued prior to disease progression, patients in the combination arm should be continued on Apatorsen (OGX-427) single agent therapy until disease progression unless there is evidence of unacceptable toxicity, patient withdrawal of consent or termination of the study, whichever occurs first. All patients will be followed for disease progression. Tumour evaluations will be performed before the initiation of treatment and every 6 weeks during and after completion of chemotherapy. Once disease progression is documented, patients will enter a Survival Follow-up Period during which data will be collected every two months regarding further cancer therapy, secondary malignancy and survival status. The study will also assess the relationship between the anticipated anti-tumour activity of the treatment regimen and biological characteristics of patients' tumours at baseline.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria: 1. Written informed consent prior to admission to this study 2. Histologically confirmed squamous cell lung cancer. Patients with adenosquamous or mixed histology are not eligible for this study. 3. Stage IIIB disease that is unsuitable to radio-chemotherapy or Stage IV disease or recurrent NSCLC; recurrent disease must not be amenable to resection or radical radiotherapy with curative intent. 4. Patients must have:

- at least one lesion, not previously irradiated, that can be measured accurately

at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) OR

- lytic or mixed (lytic + sclerotic) bone lesions in the absence of measurable

disease as defined above 5. Willing to donate archival diagnostic tissue for translational research, if available. 6. Haematologic and biochemical indices within the ranges shown below. These measurements must be performed within one week prior to randomisation

- ANC ≥1. 5 x 109/L;, platelet count ≥100 x 109/L,

- Serum creatinine < 1. 5 times the upper limit of normal (ULN)

- Bilirubin level < 1. 5 X ULN

- AST or ALT <3. 0 X ULN or <5 X ULN in the presence of liver metastases

7. ECOG performance status 0-2 8. Non-childbearing potential (i. e., physiologically incapable of becoming pregnant) 9. Male or Female aged ≥18 years Exclusion Criteria: 1. Symptomatic CNS involvement or CNS involvement requiring steroid therapy; patients with treated brain metastases that are asymptomatic and have been clinically stable for 1 month will be eligible for protocol participation 2. Previous systemic treatment for lung cancer (exception for patients with recurrent disease: adjuvant chemotherapy is allowed as long as this was finished at least 1 year prior to enrolment and did not contain gemcitabine) 3. Known tumour EGFR mutation, unless contraindication to EGFR-directed therapy 4. Known tumour ALK rearrangements, unless contraindication to Alk-directed therapy or Alk-directed therapy not available 1 5. Pre-existing sensory or motor polyneuropathy >Grade 2 according to NCI CTCAE 6. Significant cardiovascular disease, such as

- History of myocardial infarction, acute coronary syndromes (including unstable

angina), or history of coronary angioplasty/stenting/bypass grafting within past 6 months.

- History of symptomatic congestive heart failure (CHF) New York Heart Association

(NYHA) Classes III-IV.

- Severe cardiac arrhythmia requiring medication or severe conduction


- Poorly controlled hypertension (resting diastolic blood pressure >115 mmHg)

- Clinically significant valvular disease, cardiomegaly, ventricular hypertrophy,

or cardiomyopathy 7. Active second malignancy (except non-melanomatous skin cancer): active secondary malignancy is defined as a current need for cancer therapy or a high possibility (>30%) of recurrence during the study. 8. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study entry. 9. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent. 10. Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol.

Locations and Contacts

Christine James, Phone: 02078828490, Email: CEDAR@qmcr.qmul.ac.uk

Heart of England NHS Foundation Trust, Birmingham B9 5SS, United Kingdom; Not yet recruiting
Shobhit Baijal, Email: shobhit.baijal@heartofengland.nhs.uk
Shobhit Baijal, Principal Investigator

Sandwell and West Birmingham Hospitals NHS Trust, Birmingham B18 7QH, United Kingdom; Not yet recruiting
Qamar Ghafoor, Email: qamar.ghafoor@uhb.nhs.uk
Qamar Ghafoor, Principal Investigator

Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust, Bournemouth BH7 7DW, United Kingdom; Not yet recruiting
Tom Geldart, Email: tom.geldart@rbch.nhs.uk
Tom Geldart, Principal Investigator

University Hospitals Bristol NHS Trust, Bristol BS2 8ED, United Kingdom; Not yet recruiting
Jeremy Braybrooke, Email: jeremy.braybrooke@uhbristol.nhs.uk
Jeremy Braybrooke, Principal Investigator

East Kent Hospitals University NHS Foundation Trust, Canterbury CT1 3NG, United Kingdom; Not yet recruiting
Mathilda Cominos, Email: mathilda.cominos@nhs.net
Mathilda Cominos, Principal Investigator

Velindre Cancer Centre, Cardiff CF14 2TL, United Kingdom; Not yet recruiting
Jason Lester, Email: jason.lester2@wales.nhs.uk
Jason Lester, Principal Investigator

Colchester Hospital University NHs Foundation Trust, Colchester CO3 3NB, United Kingdom; Not yet recruiting
Dakshinamoorthy Muthukumar, Email: muthu.kumar@colchesterhospital.nhs.uk
Dakshinamoorthy Muthkumar, Principal Investigator

Dartford and Gravesham NHS Trust, Dartford DA2 8DA, United Kingdom; Not yet recruiting
Riyaz Shah, Email: riyaz.shah@nhs.net
Riyaz Shah, Principal Investigator

Betsi Cadwaladr University Health Board, Denbighshire LL18 5UJ, United Kingdom; Not yet recruiting
Angel Garcia, Email: angel.garcia@wales.nhs.uk
Angel Garcia, Principal Investigator
Cath Bale, Principal Investigator

Royal Devon & Exter NHs Foundation Trust, Exeter EX2 5DW, United Kingdom; Not yet recruiting
Liz Toy, Email: liz.toy@nhs.net
Liz Toy, Principal Investigator

Royal Surrey County Hospital NHS Foundation Trust, Guildford GU2 7XX, United Kingdom; Not yet recruiting
Marianne Illsley, Email: m.illsley@nhs.net
Marianne Illsley, Principal Investigator

Leeds Teaching Hospitals NHS Trust, Leeds LS9 7TF, United Kingdom; Not yet recruiting
Clive Mulatero, Email: clive.mulatero@leedsth.nhs.uk
Clive Mulatero, Principal Investigator

Barts Health NHS Trust, London EC1M 6BQ, United Kingdom; Recruiting
Farah Louise Lim, Email: farahlouise.lim@bartshealth.nhs.uk
Farah Louise Lim, Principal Investigator

Chelsea and Westminster Hospital NHS Foundationh Trust, London SW10 9NH, United Kingdom; Not yet recruiting
Tom Newsom-Davis, Email: tom.newsom-davis@chelwest.nhs.uk
Tom Newsom-Davis, Principal Investigator

Imperial College Healthcare NHS Trust, London W6 8RF, United Kingdom; Not yet recruiting
Conrad Lewanski, Email: conrad.lewanski@imperial.nhs.uk
Conrad Lewanski, Principal Investigator

University College London Hospitals NHS Foundation Trust, London NW1 2PG, United Kingdom; Not yet recruiting
Siow Ming Lee, Email: siow-ming.lee@uclh.nhs.uk
Siow-Ming Lee, Principal Investigator

Maidstone and tunbridge Wells NHS Trust, Maidstone ME16 9QQ, United Kingdom; Not yet recruiting
Riyaz Shah, Email: riyaz.shah@nhs.net
Riyaz Shah, Principal Investigator

The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom; Not yet recruiting
Fiona Blackhall, Email: fiona.blackhall@christe.nhs.uk
Fiona Blackhall, Principal Investigator

Nottingham University Hospitals NHS Trust, Nottingham NG5 1PB, United Kingdom; Not yet recruiting
Sally Morgan, Email: sally.morgan@nuh.nhs.uk
Sally Morgan, Principal Investigator

Royal Berkshire NHS Foundation Trust, Reading RG1 5AN, United Kingdom; Not yet recruiting
Joss Adams, Email: joss.adams@royalberkshire.nhs.uk
Joss Adams, Principal Investigator

Abertawe Bro Morgannwg University Health Board, Swansea SA2 8QA, United Kingdom; Not yet recruiting
Kath Rowley, Email: kath.rowley3@wales.nhs.uk
Kath Rowley, Principal Investigator

Additional Information

Starting date: June 2014
Last updated: April 17, 2015

Page last updated: August 23, 2015

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